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Uterine cancer is the most common gynecologic malignancy in the United States. Annually there are approximately 46,470 new cases diagnosed each year.  Incidence rates are higher in whites than in black, Hispanic or Asian/Pacific Islander women.

Women have a 2.5 percent lifetime risk of developing endometrial cancer, which accounts for 6 percent of all cancers in women. Fortunately, most cases are diagnosed at an early stage when surgery alone may be adequate for cure. Five-year survival rates for localized, regional, and metastatic disease are 96, 67, and 17 percent, respectively.

Two Main Types of Endometrial Cancer:

Differences in epidemiology and prognosis suggest that two forms of endometrial cancer exist: those related to and those unrelated to estrogen stimulation

-Type I endometrial carcinoma is estrogen-related, usually presents histologically as a low grade endometrioid tumor, and is associated with atypical endometrial hyperplasia. These patients tend to have risk factors such as obesity, nulliparity, endogenous or exogenous estrogen excess, diabetes mellitus, and hypertension.

Type II endometrial carcinomas appear unrelated to estrogen stimulation or endometrial hyperplasia, and tend to present with higher grade tumors or poor prognostic cell types, such as papillary serous or clear cell tumors. These patients are often multiparous, and do not have an increased prevalence of obesity, diabetes, or hypertension. They also tend to be older than women with endometrioid tumors.

Risk Factors of Endometrial Cancer:

Long-term estrogen exposure

Exogenous estrogen — Treatment of postmenopausal women with estrogen therapy provides significant short and long-term benefits by reducing hot flashes and vaginal dryness and maintaining bone density. Treatment with estrogen alone, however, increases the risk for endometrial hyperplasia and carcinoma.

The excess risk of endometrial hyperplasia and carcinoma can be significantly reduced by the concomitant administration of progestins.

Endogenous estrogen — Excessive endogenous conversion of adrenal precursors to estrone and estradiol by adipose cells and endogenous estrogen production from functional ovarian tumors are associated with an increased risk of endometrial cancer; conversion of adrenal precursors to estrone is far more common than functional ovarian tumors.

Tamoxifen use — Tamoxifen is a competitive inhibitor of estrogen binding to estrogen receptors that also has partial agonist activity (ie, tamoxifen is a weak estrogen). It is used for therapy in women with early stage breast cancer, as treatment for recurrent disease, and for reduction of breast cancer incidence in high-risk women. The site-specific activity of tamoxifen in different tissues is well recognized, suppressing the growth of breast tissue, but also stimulating the endometrial lining. Tamoxifen use has been linked to development of endometrial pathology, both benign and malignant

Obesity and Endometrial Cancer - Higher BMI is also associated with endometrial cancer presenting at less than 45 years of age

One explanation for these findings is that obese women have high levels of endogenous estrogen due to the conversion of androstenedione to estrone and the aromatization of androgens to estradiol, both of which occur in peripheral adipose tissue. Unlike some other disorders, however, the risk of developing endometrial cancer is not related to the distribution of adipose tissue

Chronic anovulation — The normal menstrual cycle is characterized by cyclic changes in pituitary and gonadal hormones. Many women with chronic anovulation have an adequate amount of biologically active estrogen since androgens can be converted peripherally to estrogens in the absence of normal ovarian function; however, their anovulatory cycles lack the progesterone secretion normally present in the luteal phase. The classic example is women with polycystic ovary syndrome (PCOS) who are hyperandrogenic at baseline. These women have constant estrogenic stimulation of the endometrium leading to endometrial hyperplasia and, in some cases, endometrial cancer. In fact, the majority of cases of endometrial cancer in young women occur in association with PCOS

Familial predisposition and genetics — A familial tendency toward isolated endometrial cancer has been suggested for first degree relatives, although no candidate genes have been identified consistently. Other familial associations with endometrial cancer include:

Lynch syndrome — In women with Lynch syndrome (hereditary nonpolyposis colorectal cancer), the lifetime risk of endometrial cancer is 27 to 71 percent compared with 3 percent in the general population. The mean age at endometrial cancer diagnosis in women with Lynch syndrome is 46 to 54 years, compared with a mean age of 60 years in other women. The majority of Lynch syndrome-associated endometrial cancers are endometrioid histology and present at an early stage, similar to sporadic endometrial cancer. Women with Lynch syndrome are also at an elevated risk of colon and ovarian cancer, along with other malignancies

Protective Factors Against Endometrial Cancer:

Hormonal contraceptives — The use of OCs decreases the risk of endometrial cancer by 50 to 80 percent. In a classic study, women using combination OCs for at least 12 months had a relative risk of endometrial cancer of 0.6 (95% CI 0.3-0.9) compared to nonusers. The protective effect persisted for at least 15 years after cessation of use.

This benefit is likely related to the progestin component of OCs, which suppresses endometrial proliferation. There are no data regarding endometrial cancer protection with non-oral estrogen-progestin contraceptives (ring, patch). Other types of hormonal contraception that include progestins provide endometrial protection against development of neoplasia

DIAGNOSIS — Endometrial cancer is a histological diagnosis; therefore tissue must be obtained.

Endometrial sampling — We prefer endometrial biopsy as the initial diagnostic test to rule out endometrial cancer. A blind endometrial biopsy performed in the office setting using a Pipelle sampling device is simple to perform, does not require anesthesia, and is generally well tolerated by the patient. This procedure has high sensitivity, a low complication rate, and low cost.

Staging of Endometrial Carcinoma:

Staging uterine carcinoma∆ (TNM and International Federation of Gynecology and Obstetrics [FIGO])

Note: cTNM is the clinical classification, pTNM is the pathologic classification.

5 Year Survival PROGNOSIS of Endometrial Cancer Based on Stage of Endometrial Cancer:

A stratification of five-year survival outcomes using the newer 2010 FIGO/AJCC TNM staging criteria is as follows:

• Stage IA – 89.6 percent
• Stage IB – 77.6 percent
• Stage II – 73.5 percent
• Stage IIIA – 56.3 percent
• Stage IIIB – 36.2 percent
• Stage IIIC1 – 57 percent
• Stage IIIC2 – 49.4 percent
• Stage IVA – 22 percent
• Stage IVB – 21.1 percent

Treatment of Endometrial Carcinoma:

            -The treatment of early stage, low grade endometiral carcinoma is surgery.

-We recommend total extrafascial hysterectomy with bilateral salpingo-oophorectomy performed either via laparotomy or laparoscopy for staging and initial management of endometrial carcinoma

-Women with apparent stage IA grade 1 endometrial carcinoma who wish to preserve fertility can opt to avoid TAH-BSO and undergo progestin therapy, but the optimum surveillance of these women is not known and they are at risk for recurrent and synchronous disease. Thus, we recommend that these women undergo TAH-BSO after completion of childbearing, even in cases with demonstrated tumor regression We suggest surgical cytoreduction in women who are found to have advanced disease at exploration

-The status of both the pelvic and paraaortic lymph nodes should be assessed intraoperatively in all patients. Given the importance of identification of nodal metastases to staging and treatment decisions, this assessment should be performed by experienced surgeons, such as gynecological oncologists

-We suggest lymph node removal for most women with apparent stage I endometrial carcinoma.

-For women with stage II endometrial carcinoma, we suggest performing a simple hysterectomy (extrafascial class I) with lymphadenectomy rather than radical hysterectomy. The exceptions to this are women with gross cervical involvement in whom performing a simple hysterectomy would cut through the tumor (all gross disease should be removed) and/or those in whom it is uncertain whether the primary is cervical or uterine.

-For women with low-risk endometrioid endometrial cancer that is confined to the endometrium, adjuvant therapy is not indicated.

-For resected low-intermediate risk disease, observation or vaginal brachytherapy are both acceptable postsurgical options. The main benefit of vaginal brachytherapy is to reduce local recurrence rates.

-For women with high-intermediate risk uterine cancer, we recommend adjuvant RT to reduce the risk of a local recurrence.  For most patients, we recommend vaginal brachytherapy rather than pelvic RT, because locoregional control can be achieved with a more favorable short-term and long-term toxicity.

-For women with high-risk uterine cancer with extrauterine disease extension (stage III or IV disease), we recommend adjuvant chemotherapy rather than RT alone. The optimal chemotherapy regimen has not been established. Pending the results of GOG 209, we use the TAP regimen (doxorubicin plus cisplatin and paclitaxel), although others prefer cisplatin plus doxorubicin or carboplatin plus paclitaxel.

-We suggest adding adjuvant pelvic RT to chemotherapy for improved local control.

Here Dr. Tony Talebi discusses “What is the treatment of Endometrial Carcinoma?” with Dr. Aaron Wolfson, vice chairman of Radiation Oncology at the University of Miami.   The discussion includes Endometrial cancer prognosis, what causes endometrial cancer, signs of endometrial cancer, endometrial cancer symptoms, endometrials cancer, endometrial cancer stage 4, treatment of endometrial cancer, endometrial cancer association, stage four endometrial cancer, small cell endometrial cancer, symtoms of endometrial cancer, causes of endometrial cancer, endometrial cancer chemotherapy, what is endometrial cancer, endometrial cancers, endometrial cancer information, endometrial cancer prevention, stage 4 endometrial cancer, information about endometrial cancer, stage iv endometrial cancer, endometrial cancer signs, endometrial cancer symptom, is endometrial cancer curable, stage 3b endometrial cancer, endometrials cancer symptoms, survival rates for endometrial cancer, symptoms of endometrial cancer, endometrial cancer survivors, endometrial cancer symptons, endometrial cancer survival, treatments of endometrial cancer, symptons of endometrial cancer, endometrial cancer statistics, non small cell endometrial cancer, chemo for endometrial cancer, endometrial cancer survival rate, large cell endometrial cancer, effects of endometrial cancer, endometrial cancer screening, endometrial cancer diagnosis, endometrial cancer societ endometrial cancer clinical trials, endometrial cancer metastasis, survival rate endometrial cancer, symptom of endometrial cancer, info on endometrial cancer, new treatments for endometrial cancer, how common is endometrial cancer

Dr. Aaron Wolfson’s Credentials:

Education

After receiving his M.D. from the University of Florida , Aaron Wolfson did his internship at the University of Miami and his residency in radiation oncology at the Medical College of Virginia in Richmond . Immediately upon completion of his residency, he joined the faculty of the University of Miami-School of Medicine's Department of Radiation Oncology as an instructor. From 1995–2003, Wolfson served as director of the department's residency training program.

Now a full tenured, Professor of Radiation Oncology, Dr. Wolfson maintains a secondary appointment as professor in the Department of Obstetrics and Gynecology. He is nationally and internationally recognized for his work in malignant tumors of the female genital tract. He is also nationally known for his expertise in both benign and malignant tumors of the bone and soft tissue.